Estrogens effect brain dopaminergic systems, as shown by their ability to potentiate haloperidol-induced catalepsy in rats, to prevent apomorphine-induced stereotypies in rat, and ameliorate tardive dyskinesias induced by prolonged DOPA administration in man. The striato-nigral GABAargic system not only subserves the feedback regulation of nigro-striatal dopaminergic neurons, but also is considered the main output system for dopamine related messages of striatal origin. Repeated estradiol benzoate administrations reduce both nigral and striatal GABA concentration, and decreases the rate of GABA accumulation in the nigra induced by gabaculine, a GABA-transaminase inhibitor. This decrease of GABA turnover may be operative in the anti-dyskinetic action of estrogens in man. A separate GABAergic system projects from the arcuate nucleus of the hypothalamus to the external layer of the median eminence. GABA released from this tubero-infundibular pathway into the portal circulation acts on pituitary receptors to inhibit prolactin release. Estrogens are involved in prolactin regulation. We have found that repeated, but not a single administration of estradiol benzoate increase anterior pituitary GABA content, dramatically. Probably this is associated with an increase of GABA release from the tuberoinfundibular system. Consistent with this hypothesis, repeated estrodiol benzoate administration increases the Vmax of glutamate decarboxylase (the enzyme which forms GABA) in the median eminence, although the Km for the substrate (glutamate) is not changed.